2-Hydroxybenzoylaminothiazole derivatives having a hydroxy group at the 2-position on the benzene ring are known to have effects for the improvement of gastrointestinal dysmotility, which makes them useful as preventive or therapeutic drugs for various types of gastrointestinal dysmotility (WO96/36619). Among such 2-hydroxybenzoylaminothiazole derivatives, 2-[N-(4,5-dimethoxy-2-hydroxybenzoyl)amino]-4-[(2-diisopropylaminoethyl)am inocarbonyl]-1,3-thiazole has particularly excellent effects for the improvement of gastrointestinal dysmotility and thus is useful as a pharmaceutical.
According to the descriptions of the above-described WO96/36619, the 2-hydroxybenzoylaminothiazole derivative is produced through the following procedure. 2-Hydroxybenzoic acid serving as a raw material is subjected to condensation reaction with 2-amino-4-alkoxycarbonyl-1,3-thiazole (step 1). Subsequently, the alkoxycarbonyl group of the thiazole ring is further subjected to amidation (step 2).
However, when the carboxy group of 2-hydroxybenzoic acid is activated by use of a condensing agent or a halogenating agent so as to perform the above-described step 1 reaction, reaction such as polymerization frequently occurs, so make production of the target product difficult. To avoid this problem, a conceivable method in the case of amidation of 2-hydroxybenzoic acid (step 1) is as follows. The hydroxy group at the 2-position of the benzene ring of 2-hydroxybenzoic acid (hereinafter referred to as "the 2-hydroxy group") is protected and then reacted with a compound having an amino group, after which, deprotection is performed. Examples of the protective group for the 2-hydroxy group used in the present method include known protective groups such as an alkyl group, an allyl group, a benzyl group, a tetrahydropyranyl group, and a silyl group. Of these, an alkyl group is generally used. For deprotection, a known dealkylation reaction may be performed (conversion of an alkoxy group into a 2-hydroxy group). Examples of known dealkylation reactions include those by use of acidic reagents including Br.phi.nsted acids such as hydrobromic acid, hydriodic acid, and trifluoroacetic acid, Lewis acids such as boron tribromide and aluminum chloride (frequently used singly or in combination with alkyl sulfurs), pyridine hydrochloride, and hydrobromic acid-acetic acid solution; reactions by use of alkaline reagents such as sodium methoxide, sodium cyanide, lithium diphenylphosphine, and lithium chloride; reactions by use of silicon reagents such as trimethylsilyl iodide; and hydrogenation reduction such as catalytic reduction.
However, through these known deprotection reactions, selective dealkylation at the 2-position is difficult for a compound having a substituent such as an alkoxy group or an ester group at a position other than the hydroxy-protected 2-position of the benzene ring at which hydroxy is protected (hereinafter referred to as "the 2-protected hydroxy group"). In addition, particularly in the case of a reaction by use of an alkaline reagent, solvolysis and a side reaction attributable to a base may occur, and, when there is employed an N-thiazolyl-2-substituted benzamide compound containing a catalyst poison such as sulfur atoms in the substrate, hydrogenation reduction cannot be completed. Therefore, there is still need for a process for efficiently producing a 2-hydroxybenzamide derivative, in which the 2-protected hydroxy group is selectively dealkylated without affecting other substituents on the benzene ring and without causing any side reaction.